Nanostream, Inc.

Steven E Hobbs

Christoph D Karp

Marci Pezzuto

Paren P Patel

Joseph F Covington

Stephen D O'Connor

Matthew M Gregori

Eugene Dantsker

Jeffrey Alan Koehler

Scott G Beach

Hau H Duong

Ronald C Gamble

Mark S Scheib

Courtney Coyne

Chromatographic separation devices include multiple batch-processed columns joined by a body structure and adapted to perform parallel analyses. Both slurry-packed and monolithic column embodiments are provided. One or more liquid-permeable frits of various types may be used to retain stationary phase material within columns. A fluidic distribution network may be used to distribute stationary phase material and/or mobile phase solvents to multiple columns. Separation devices, including microfluidic embodiments, may be fabricated with various materials including polymers. Multi-column fabrication and separation methods are provided.

Multi-column separation devices and methods

Systems and methods for analyzing a plurality of samples in parallel include a plurality of liquid phase separation regions, a plurality of microfluidic storage regions, and a common mass spectrometer. Samples are separated in parallel in the separation regions to yield a plurality of output streams that are stored in the storage regions. The contents of each storage region, or at least a representative portion thereof, are sequentially discharged, ionized, and directed to the inlet of a mass spectrometer. In this manner, multiple separations are conducted in parallel with outputs provided serially to a common mass spectrometer without any loss of data. Microfluidic storage regions minimize diffusion between bands of separated samples. Portions of separated samples may be directed to fraction collectors.

Systems and methods for high throughput sample analysis

A threadless interface for a fluidic system includes a microfluidic device having an outer surface and an internal near-surface channel having a first width and disposed at a first depth relative to the outer surface, with the first width being less than about two times the first depth. A fluidic seal engages the outer surface and exerts an elevated contact pressure against at least a portion of the outer surface without substantially occluding the channel. A preferred seal includes a raised boss. A fault tolerant flow path design can accommodate misalignment between adjacent device layers without detrimentally affecting fluid flow capability. The interface may be used in a microfluidic system for performing parallel analyses such as high performance liquid chromatography.

Sealing interface for microfluidic device

Systems for analyzing multiple samples in parallel using mass spectrometric preferably coupled with fluid phase separation techniques are provided. A multi-analyzer mass spectrometer includes multiple inlets, multiple mass analyzers, and multiple transducers to conduct mass analyses of multiple samples in parallel. A modular mass analyzer may include a vacuum enclosure, a chassis, and multiple mass analysis modules disposed within the chassis. Modules are preferably disposed in a spatially compact two-dimensional array. A common multi-stage vacuum system may be utilized in conjunction with baffles or partitions disposed within and between modules to maintain differential vacuum conditions within the spectrometer utilizing a minimum number of pumps. Common control inputs may be provided to multiple modules or other components within a multi-analyzer spectrometer. Fluid phase separation devices for use with a multi-analyzer spectrometer may be microfluidic devices utilizing chromatographic, electrophoretic, or other separation methods.

High throughput systems and methods for parallel sample analysis

High throughput liquid chromatography systems include multiple separation columns and multiple flow-through detection regions in sensory communication with a common radiation source and a multi-channel detector. Preferred detector types include a multi-anode photomultiplier tube, a charge-coupled device detector, a diode array, and a photodiode array. In certain embodiments, separation columns are microfluidic and integrated into a unitary microfluidic device. The optical path through a detection region is preferably coaxial with the path of eluate flow along a flow axis through a detection region. On-board or off-board detection regions may be provided.

Parallel detection chromatography systems

Systems and methods for performing multiple parallel chromatographic separations are provided. Microfluidic cartridges containing multiple separation columns allow multiple separations to be performed in a limited space by a single instrument containing high-pressure pumps and analyte detectors. The use of pressure fit interfaces allows the microfluidic cartridges to easily be removed and replaced within the instrument, either manually or robotically.

System and method for performing multiple parallel chromatographic separations

Pressure-driven microfluidic separation devices, such as may be used for performing high performance liquid chromatography, are provided. Multiple separation columns may be defined in a single device and packed with stationary phase material retained by porous frits. One or more splitters may be provided to distribute slurry and/or mobile phase among multiple separation columns. In one embodiment, separation devices are substantially planar and fabricated with multiple device layers. Systems and methods employing slurry for packing separation devices are also provided.

Separation column devices and fabrication methods

Modular microfluidic systems includes a plurality of microfluidic modules, each capable of performing fluidic operations including, but not limited to, filtering, splitting, regulating pressure, mixing, metering, reacting, diverting, heating, cooling, and condensing are provided. The microfluidic modules are polymeric, stencil-based structures adapted to be coupled in sequence for performing biological or chemical synthesis, including, but not limited to, chemical and biological syntheses of organic, polymer, inorganic, oligonucleotide, peptide, protein, bacteria, and enzymatic products.

Microfluidic analytical devices and methods

A flow cell for performing optical analysis of a fluid is provided. The flow cell comprises a monolithic cell housing that defines a detection chamber, fluid inlet and outlet ports and illumination and detection ports. Optical fibers are inserted in the illumination and detection ports, thereby forming substantially fluid-tight seals. A flow cell may be press-fit against a microfluidic device, with fluid sealing aided by O-rings.

Flow cell for optical analysis of a fluid

A method for fabricating a microfluidic device where first and second substantially flat platens are provided. Multiple substantially planar, substantially metal-free, adhesiveless polymer device layers, the device layers including a first cover layer, second cover layer, and at least one stencil layer defining a microfluidic channel penetrating through the entire thickness of the stencil layer also are provided. Each stencil layer is disposed between other device layers such that the channel is bounded laterally by a stencil layer, and bounded from above and below by surrounding device layers to define an upper channel surface and a lower channel surface. The device layers are stacked between the first platen and the second platen. The stacked device layers are controllably heated according to a heating profile adapted to form a substantially sealed adhesiveless microfluidic device wherein each upper channel surface remains distinct from its corresponding lower channel surface. The resulting microfluidic device has high inter-layer bond strength while preserving the integrity of the channel(s) defined in the stencil layer(s).

Adhesiveless microfluidic device fabrication

Systems and methods for collecting the output of multiple simultaneously operated chromatography columns and providing the outputs to a single mass spectrometer are provided. Such systems utilize predetermined lengths of microfluidic tubing that act as storage buffers for the substantially all of the output of each column, preserving all data and, because the storage buffers are microfluidic, there is minimal diffusion between sample bands and solvent and signal clarity is preserved.

Systems and methods for high-throughput microfluidic sample analysis

A microfluidic reactor for performing chemical and biological synthesis reactions, including chemical and biological syntheses of organic, polymer, inorganic, oligonucleotide, peptide, protein, bacteria, and enzymatic products is provided. Two fluids are input into the device, mixed in a mixing region and provided to a long, composite reaction channel. Fluids flowing through the reaction channel may be diverted at a diversion region into a sample channel. Fluids in the sample channel may be mixed at a second region, with additional reagents.

Microfluidic synthesis devices and methods

Microfluidic devices for splitting an established fluidic flow through a microfluidic channel among multiple downstream microfluidic channels include a plurality of elevated flow resistance regions to promote precise and predictable splitting. Each elevated resistance region imparts a flow resistance that is substantially greater than the characteristic resistance to established flow of its associated downstream channel. Elevated flow resistance regions may include one or more porous materials and/or alterations to the channel geometry of at least a portion of a downstream channel.

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West Hills, CA, United States of America

Steven E Hobbs